Cancer Research UK funded PhD studentship: Does regulation of inflammatory cytokines play a role in the cancer-preventative actions of aspirin?
Application Deadline: 19 August 2018
Start Date: October 2018
Applications are invited from graduates with a BSc (First or Upper Second) or MSc (Distinction), or equivalent, to work within the Centre for Cancer Prevention. This 4-year studentship will commence in October 2018 and will be based at the Charterhouse Square Campus. This is an exciting opportunity for a graduate from disciplines related to Molecular epidemiology.
Supervisors: Professor Fran Balkwill & Dr Belinda Nedjai
This project will combine population and cancer biology research using both ‘in silico’ and ‘wet lab’ research. The hypothesis to be investigated is that aspirin prevents cancer by inhibiting key tumour-promoting cytokines either systemically or in undetectable pre-cancerous lesions. A large amount of data show that inflammatory cytokines promote early stages of experimental cancer development but there is little information from human cancer studies.
Key questions to be answered in this project:
1. Are elevated systemic levels of inflammatory cytokines such as IL-6 predictive of subsequent cancer development?
2. Are inflammatory cytokines systemic biomarkers of aspirin action?
3. Does aspirin reduce tumour-promoting inflammatory cytokine production
Working with colleagues in the Wolfson Institute, the student will conduct a meta-analysis of the literature on plasma/serum cytokines and cancer susceptibility in population cohorts. Some inflammatory cytokines, especially IL-6, have predictive value in population-based cancer studies with cohort studies associating elevated blood levels of IL-6 with increased cancer risk.
Working in the Centre for Cancer and Inflammation, the student will measure inflammatory cytokine levels in plasma and other body fluids pre-and post- aspirin dosing in trials involving both cancer patients and normal control individuals. For the assays, we will use MesoScale Discovery™ (MSD) multiplex assays that have detection limits in low pg/high fg levels. A 40 analyte cytokine multiplex will be used in the first instance.
One set of samples will come from a prospective randomized clinical trial. Only the biomarker studies will be funded through the Catalyst award. 150 healthy men and 150 women with average BMI of 23-26 aged between 45-75 years will be enrolled and consented. 100 volunteers will have previously taken aspirin for at least one year before enrolment and 200 volunteers will never have taken aspirin. The latter group will receive either 100mg of aspirin or placebo once daily for a period of twelve months while those who previously received aspirin for at least one year will continue aspirin therapy at 100 mg daily. We will collect blood, urine and saliva samples at the start of the trial (base line), after 3 months and at 12 months. Specific timing of blood sampling in relation to aspirin intake will be respected. All plasma samples will be taken within a two hour-time window and processed according to an SOP validated in clinical trials. We have extensive experience over the past 15 years of measuring inflammatory cytokines and chemokines in plasma samples from cancer patients and normal controls. Some of these studies have been conducted as part of Phase I and II clinical trials of biological therapies in advanced cancer and others in retrospective analyses e.g. studying the effects of chemotherapy on plasma cytokine levels. Matched pre- and post (8 weeks) treatment plasma samples from participants in the ADD-Aspirin trial will also be studied.
Results from these studies will be integrated with methylation profiling and transcriptomic data that will be conducted on DNA and RNA from the same blood samples by Belinda Nedjai’s group, using the machine learning approach described in the AsCAP application. Recent experience from the Balkwill lab of integrating multiple datasets from tumour microenvironment studies may also be useful.
Who should apply
Academic Entry Requirements
These studentships are open to graduates with either:
- a BSc with a first of upper second; or,
- an MSc with Distinction
For more information on international equivalencies please see here.
English Language Requirements
Applicants for whom English is not a first language will also require a minimum IELTS score of 6.5 (with 6.0 in the written component) or equivalent, unless your undergraduate degree was studied in, and awarded by, an English speaking country. For more information on acceptable English language qualifications please see here.
The funding for these studentships only covers applicants who are UK Nationals, EEA/Swiss migrant workers and non-UK nationals with indefinite leave to remain in the UK who will have three years ordinary residence in the EU prior to the start of the studentship. .
The studentship includes the following funding for 4 years:
- A tax free annual stipend of £21,000
- Tuition Fees at the Home/EU rate
How to apply
Your application should consist of a CV and contact details of two academic referees. You must also include a personal statement (1,000 words maximum) describing your suitability for the selected project including how your research experience and interests relate to the project.
Please submit your application to: Brenda Bell firstname.lastname@example.org
Who to contact if you require further information
Informal enquiries can be made to Professor Fran Balkwill: email@example.com